Brentuximab

• Class: Antibody–drug conjugate (ADC) – anti-CD30 monoclonal antibody linked to monomethyl auristatin E (MMAE)
• Type: IV targeted therapy.

Mechanism of Action (MOA)

1. CD30 targeting: Brentuximab binds CD30 receptors on malignant cells (e.g., Hodgkin lymphoma, anaplastic large cell lymphoma).
2. Internalization: The ADC is internalized into the cell.
3. Cytotoxic release: MMAE is released → disrupts microtubules → cell cycle arrest and apoptosis.
4. Provides targeted delivery of chemotherapy, sparing most normal cells.

Clinical Uses

• Hodgkin lymphoma: relapsed/refractory after autologous stem cell transplant or ineligible patients.
• Systemic anaplastic large cell lymphoma (sALCL): relapsed/refractory disease.
• Investigational use: other CD30-positive lymphomas, combination regimens.

Dosing (Adults)

• 1.8 mg/kg IV every 3 weeks (up to 16 cycles).
• Administer over 30 minutes; premedication not routinely required.
• Dose adjustments for:
  • Hepatic impairment (reduce in moderate/severe).
  • Renal impairment (caution in CrCl <30 mL/min).
  • Hematologic toxicity.

Toxicities

• Hematologic: neutropenia, anemia, thrombocytopenia.
• Peripheral neuropathy – cumulative, dose-limiting (MMAE-related).
• Fatigue, nausea, diarrhea.
• Infusion-related reactions – rare but possible.
• Rare: hepatotoxicity, progressive multifocal leukoencephalopathy (PML).

Monitoring

• CBC prior to each cycle.
• Neurologic assessment for peripheral neuropathy.
• Liver function tests.
• Observe for infusion reactions during and after infusion.
• Renal function in patients with pre-existing impairment.

Summary

Brentuximab (Adcetris®) is an anti-CD30 ADC delivering MMAE to lymphoma cells. Key concerns are peripheral neuropathy, myelosuppression, and infusion reactions, requiring monitoring of CBC, liver function, and neurologic status.